1. Technical Field of the Invention
This novel therapeutic (reparative, etiotropic not merely symptomatolytic) electrostimulatory method hereinafter referred to as Coupled Neuraxial Mesoscopic Desynchronization Electrostimulation Therapy (cNMDET) is comprised of a varied combination of progressively sequenced electrode placements based on the clinically determined targeted areas which are further comprised of the central nervous system (CNS) [regions of the brain, spinal cord and intervening structures including, but not limited to, the underlying (contributory) clinicopathologic mechanisms of the autonomic nervous system (ANS)] and clinically involved components of the peripheral nervous system (PNS) variably coupled as provided for by the patient-specific, controlling treatment protocol in such a manner as to apply this therapeutic electrostimulation method along the coursing path (longitudinally) of the targeted neural pathway over a segment and/or in its entirety (the full expanse possible of the CNS and PNS), as well as, the utilization of patterned applications for involved joints, muscles, fascia, ligaments, tendons and areas involved in inflammatory processes of clinical significance accomplished through the application of, preferably, but not limited to, Coupled Neuraxial Transcutaneous Electrical Nerve Stimulation (cNTENS) and Coupled Neuraxial Transcranial Direct Stimulation (ctDCSn). The phrase ‘coupled neuraxial’ herein will be used to denote the method of providing therapeutic electrostimulation, longitudinally, to the CNS (regions of the brain, spinal cord and intervening structures) including, but not limited to, the ANS and clinically involved components of the PNS and other tissues, i.e., joints, muscles, fascia, ligaments, tendons and areas involved in inflammatory processes of clinical significance, variably coupled as provided for by the patient-specific, controlling treatment protocol in such a manner as to apply the therapeutic electrostimulation along the coursing path (longitudinally) of the targeted neural pathway over a segment and/or in its entirety. Of critical importance is the incorporation of this cNMDET method approach applied to all clinically targeted areas in a highly individualized manner, which is patient by patient. Strict compliance to the controlling treatment protocol is critical to protecting a favorable outcome and guarding the ‘patient experience’. The progressive sequencing of electrode placements in each controlling treatment protocol is based on the arduous clinical identification of all the clinically involved areas and, to the extent they are clinically contributive to the patient's underlying etiologic mechanisms as well as those contributing to their perception of pain, if different, in such a manner as to achieve ‘true remediation’ not ‘merely adaptive recovery’ or simply the masking of the perception of pain. The capacity to target the reversal of maladaptive neuroplastic/metaplastic changes that subserve, in part or in whole, pain, as well as, other contributing processes (clinicopathologic mechanisms), including, but not limited to, inflammatory responses and secondary ANS changes is one of the core achievements of this method's therapeutic value. Serving as a therapeutic portal to this method are the processes of ‘priming’ and ‘preconditioning’ which allow the body's inherent ever vigilant feedback loops capable otherwise of blocking many other therapeutic approaches to now allow the experience of reparative modulation achieved by the cNMDET method which has been individually formulated as a critical quality of each treatment protocol. Without these method patent related processes of priming and preconditioning, as well as, the subsequently progressive sequencing, individualized patterned therapeutic electrostimulatory (modulatory) formulations, the human body is innately capable of negating the intended modulation of same, by overriding the intended applied reparative neuromodulation via several processes such as ‘adaptation’.
Of equal importance to this novel method as is priming and preconditioning is the utilization of another novel component of cNMDET, the ‘Neural-Tube Technique’ (NTT). NTT is the electrostimulatory coupling of the brain, intervening neural structures and spinal cord, to include, but not be limited to, the ‘sacral outflow’ area (the cauda equina area). The anatomical expanse, i.e., distance between coupled electrodes, may be quite narrow ranging to the full incorporation of the brain's most superior/rostral extreme, coupled to the spinal cord's most inferior/caudal position of the CNS to include the anatomical area of the cauda equina (‘sacral outflow area’). This expanse would include all the potential coupled placements contained therein. It is anticipated that one or more coupled electrodes (including arrays of electrodes) throughout this expanse are to be used as provided for by the controlling treatment protocol.
In its preferred embodiment, the cNMDET method would be applied utilizing an apparatus/device such as the multifunctional Algotron, a combination Coupled Neuraxial Transcutaneous Electrical Nerve Stimulation (cNTENS) and Coupled Neuraxial Transcranial Direct Stimulation (ctDCSn) apparatus/device. This apparatus/device incorporates the mandatory utilization of multiple physiologic monitoring channels and multiple therapeutic electrostimulatory channels. This novel cNTENS/ctDCSn apparatus/device is the subject of a post-election divisional patent application.
Resulting from several decades of clinical experience, the resultant understanding is that any method application to approach delivering therapeutic (reparative) electrostimulatory modalities such as the subject matter of this method application referred to as Coupled Neuraxial Mesoscopic Desynchronization Electrostimulation Therapy (cNMDET) must address, as a practical matter, the properties of applicable neural pathway synaptic associative activity and volume related cooperativity both in sufficient levels/degrees of achievement if it claims to provide true remediation, i.e., etiotropic, as opposed to only achieving a temporizing or masking effect of the presenting symptoms, i.e., symptomatolytic. It is my belief that to the extent time is spent on symptomatic approaches at the expense of accomplishing true remediation is with that passage of time comes the increasing probability of maladaptive recovery. Further, to achieve therapeutic (reparative) modulation in the targeted CNS and/or PNS the therapeutic regimen must contemporaneously address and, in fact, incorporate the body's entire adaptive mechanistic capacity (both that of the CNS and PNS individually but of greater importance, their collective interdependent states) and the potentially significant influences of clinicopathologic neuroplastic and metaplastic changes that clinically evolve until the underlying clinicodynamics are repaired.
2. Scope of the Invention in Terms of Therapeutic Needs Fulfillment
The established utility of this patent method can best be illustrated by providing a sample range of the pain related diagnostic entities targeted to date by this method. This list is only a partial list of those diagnostic entities as it relates to pain, provided here only to help illustrate the extensive scope of application of this method patent: Chronic Pain, Neuropathic Pain, Fibromyalgia Pain Syndrome, Dysautonomia, Multiple Sclerosis (MS), Barré-Liéou Syndrome, Radiculitis/Radicular Pain Syndrome, Brachial Plexitis (Parsonage Turner Syndrome) (neurogenic, non-compressive), Myofascial Pain Syndrome, Myofascial Trigger Points, Carpal Tunnel Syndrome, Tarsal Tunnel Syndrome, Phantom Limb Pain Syndrome, Parietal Pseudothalamic Pain Syndrome, Pseudothalamic Pain Syndrome, Adhesive Capsulitis, Rotor Cuff Syndrome, Bursitis, Migraines (neurogenic), Paratrigeminal Syndrome, Trigeminal Neuralgia, Temporomandibular joint disorder (TMJD) or TMJ syndrome, Tennis Elbow (Lateral Epicondylitis), Pain secondary to Klippel-Feil Syndrome and Plantar Fasciitis.
Goethe was attributed with saying: “A man sees only what he knows”. I know our clinical outcomes: I see a future for this application as we know it or as it may be ultimately manifested through the understandings/contributions of others. At the heart of this application submission is the topic of ‘pain’, ‘persistent clinical pain’, pain that causes patients to seek treatment. Despite the scientific purview of this submission, one must never loose site of the ultimate obligation/responsibility we have to continually endeavor to improve on the ‘patient experience’ in direct appreciable terms as manifested in their quality of life experiences. The genesis of this method application were the gnawing questions: What causes the development of ‘persistent clinical pain’ appearing after only a few days post precipitating event for some patients, 7-10 days in other patients, while yet other patients report the temporal onset of the ‘persistent clinical pain’ weeks or months after a known precipitating event, if any is identifiable; and, why have the treatments for same produced such poor statistical outcomes? I am not satisfied with the almost dismissive tone that comes with: “it's individualized” with no further direct interpretation (import) to the presenting patient. Yes, I believe each patient comes with their individual set of unique genetic codes and totality of experiences, but, I believe there does exist a commonality of CNS and PNS clinical neuroplastic clinicodynamic changes that commonly occur or are recruited in the case of ‘persistent clinical pain’. It is that commonality of induced mechanistic changes in the CNS and/or PNS that this method application, along with the post-election components, were brought into existence to address. It is my most solemn prayer that this patent application will lead to the appropriate attention and assistance necessary in further developing this concept to the fullest extent of its merited potential.
This method application referred to as Coupled Neuraxial Mesoscopic Desynchronization Electrostimulation Therapy (cNMDET) addresses the critical properties of applicable neural pathway synaptic associative activity and volume related cooperativity, that must be additionally recruited, both, in sufficient levels/degrees of achievement in support of true reparative modulation of the CNS and/or PNS. The complex formulation of the priming, preconditioning and treatment phases as provided for by the controlling treatment protocol promotes this, heretofore rather illusive, therapeutic (reparative) modulation in the targeted CNS and/or PNS by, in fact, synergistically incorporating the body's entire adaptive mechanistic capacity in their individual and collective states. Additionally, cNMDET enhances the supportive underlying neurometabolic capacities of neural structure and function that are therapeutically induced resulting from the application of cNMDET and is of critical importance to sustaining the desired and therapeutically sought level of reparative processes which have been, heretofore, woefully lacking in all other therapeutic approaches.
3. Description of the Related Prior Art
It is generally well known that the application of some forms of electrical stimulation to the body of a patient in the area of soreness or pain can have a therapeutic and anesthetizing effect, although the physiological basis is not completely understood. As addressed in U.S. Pat. No. 3,835,833, the application of electrostimulation via electrodes placed on the body (without mention of intervening targeted longitudinal neural pathway electrode placements) of a patient heretofore utilizing acupuncture points or generally in the area of reported pain (independent of underlying neural structure) causing various therapeutic effects such as local anesthesia or relaxation of muscle. The present invention advances in clinical import in orders of magnitude in specificity of application and scope of effectiveness based on the novel method referred to as cNMDET.
As it pertains to the various commercially available Transcutaneous Electrical Nerve Stimulation (TENS) devices, including but not limited to, Cranial Electrical Stimulation (CES) devices, manufacturers and practitioners utilizing such devices appear to be woefully deficient and possibly clinically negligent in their apparatus/device design with their recommended treatment protocols. One of the areas of greatest concern is the absence of recommendations and/or incorporation of critically essential concomitant (contemporaneous) patient physiologic monitoring. Designed to correct for the above referenced deficiencies, our multifunctional Algotron, a combination Coupled Neuraxial Transcutaneous Electrical Stimulator (cNTENS)/Coupled Neuraxial Transcranial Direct Current Stimulation (ctDCSn) apparatus/device, is the subject of a post-election divisional patent to be subsequently filed. Our multifunctional Algotron apparatus/device is, in part, comprised of a novel electrostimulatory therapeutic capacity and incorporates a comprehensive range of ‘in-process’ (real-time) contemporaneous physiologic diagnostics and monitoring channels allowing for the most effective application of cNMDET. Further, the Algotron is designed to produce true remediation, targeting etiotropic changes, not merely perpetuating one more of the many producing iatrogenic dependences on modalities that can only be viewed as being simply temporizing, masking or symptomatolytic.
The first modern, patient-wearable TENS was patented in the United States in 1974. [U.S. Pat. No. 3,817,254] It was initially used for testing the tolerance of chronic pain patients to electrical stimulation before implantation of electrodes in the spinal cord dorsal column. [Surg Neurol 2 (1): 39-40] The electrodes were attached to an implanted receiver, which received its power from an antenna worn on the surface of the skin. Of major concern for this device is the morbidity/mortality associated with required surgical implantation. This concern is addressed with the cNMDET method in that there is no known morbidity or mortality associated with its intended usage. Additionally, another deficiency is that as conceived there is no concomitant (contemporaneous) patient physiologic monitoring capacity once the patient becomes ambulatory in the post-insertion phase. Lastly, there is no provision for the treatment of the entire potentially involved neural pathway especially when the patient's condition, as is frequently seen, involves central sensitization, secondary inflammatory processes, etc. imposing secondary clinicopathologic neuroplastic and metaplastic processes which is of critical importance in guarding the clinical evolution and eventual outcome of each case.
Heretofore, generally, electrostimulatory approaches for the treatment of pain are thought to work in some combination of two basic mechanisms. First, on a high frequency, by selectively stimulating certain ‘non-pain’ nerve fibers to send signals to the brain that is thought to ‘block’ [essentially masking the pain signals by altering the perception of pain without any therapeutic (etiotropic) import] other nerve signals carrying pain messages. The claim of this approach is relatively common despite hard science indicating reported negative side-effects such as those of excitotoxicity, encouragement of a range of secondary maladaptive neuroplastic/metaplastic changes (including, but not limited to, ‘kindling’ and ‘dynamic entrainment’). Second, on low frequencies, TENS is thought to transiently stimulate the production of endorphins, the body's natural pain-relieving hormones. Historically and generally, the device was usually used for 30 minutes, several times a day on average, and was controlled by the user rather than a licensed health professional which for obvious clinical reasons is thought by many in a position to evaluate same to be contraindicated because of the lack of continuous supervision. In light of the aforementioned deficiencies, the typical range of claims made for these devices and related methodology is so conspicuously vast as to require additional due diligence by all potentially or currently subscribing practitioners and the targeted patient population at large before applying same. One supporting example of escalating concerns pertaining to the methodology, as well as, the device's design of Cranial Electrotherapy Stimulation (CES) is the published finding of the Federal Drug Administration (FDA). Noteworthy is the specific reference therein of applicability to the exclusion of Transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS) for which the cNMDET method was ideally designed. Compelling are the statements found in the below excerpt from the FDA Executive Summary prepared for the meeting of the Neurologic Devices Panel pertaining to CES, but to be clear, not ‘tDCS’ which includes our multifunctional Algotron, a combination cNTENS and ctDCSn novel apparatus/device.                “Among studies that reported a clinical benefit of CES, few can be considered rigorous, high quality clinical studies.        FDA believes that there are basic elements that should be present in any study seeking to evaluate the effectiveness of CES, including, but not limited to: randomized with a sham control group, eligibility criteria based on a specific diagnosis, a clinically relevant measure of effectiveness, adequately powered sample size, predefined success criteria, and consideration for durability of effect. None of the studies identified in the literature review met all of these criteria. Regardless of the main findings, many of these studies had key limitations in study design that likely obscure the true effectiveness of CES. For example, only 12.8% (5 of 39) of the studies reported using the DSM criteria to diagnose depression, anxiety or insomnia. Without the use of established and clinically accepted diagnostic criteria, it is unclear what psychiatric condition, if any, CES was attempting to treat in the remaining 87.2% of studies. Furthermore, the body of research lacks cohesion in the device model, dosage and duration studied. While the literature review was not limited to cleared devices, FDA sought to ensure that the output characteristics were generally consistent with the ranges of values we have evaluated in premarket submissions. In the papers that we reviewed, there were 25 different models of CES devices used, excluding 7 that were custom built and some studies did not report Page 36 of 83 the CES device model. Since the electrical output characteristics also vary across the different device types (see Table 16), making assumptions about the applicability of positive findings by one CES device to other CES devices is not possible.        Other important study limitations that have been previously mentioned include: small sample size, placebo effect (due to either no masking or unsuccessful masking) and inadequate statistical methods. In the absence of a reasonable assurance of effectiveness, a key concern stemming from our review of the literature is that use of CES in lieu of more effective, proven therapies may present undue risk to patients whose psychiatric conditions may worsen if untreated.”        
The benefit of the traditional methodology utilized by electrostimulatory devices such as a TENS device as it pertains to the treatment of pain remains, heretofore, somewhat controversial in the traditional medical community. One review from 2007 felt that the evidence supports a benefit in chronic musculoskeletal pain [Pain 130 (1): 157-165. DOI:10.1016/j.pain.2007.02.007] while another review from the Cochrane Collaboration in 2008 deemed the evidence of poor quality and thus no conclusions where possible regarding chronic pain. [Cochrane database of systematic reviews (Online) (3): CD003222] Results from a task force on neck pain, in 2008, found no clinically significant benefit to TENS for the treatment of neck pain when compared to placebo treatment. [Spine 33 (4S Supplement): S5-7. DOI:10.1097/BRS.0b013e3181643f40] A 2010 review did not find evidence to support the use of TENS for chronic low back pain. [Neurology 74 (2): 173-6 and Cochrane database of systematic reviews (Online) (4): CD003008] There is tentative evidence that it may be useful for painful diabetic neuropathy. [Neurology 74 (2): 173-6] It is for these and other reasons that the cNMDET method and Algotron apparatus/device was invented.
It is, at a minimum, noteworthy and considered by this author/inventor to be imperative for all practitioners and potentially targeted patients to be aware of the full realm of the published contraindications and warnings referenced below associated with the use of some electrostimulatory devices such as the TENS unit in the literature as of today:                This device should be used only under the ‘continuous supervision of a physician’.        Extreme caution should be exercised in patients with known myocardial disease, arrhythmias or epilepsy.        Electronic equipment such as EKG monitors and EKG alarms may not operate properly when a TENS is in use.        Also, this device should not be used over metal implants or sleep apnea monitors.        TENS, as utilized heretofore, is ineffective for pain of ‘central’ origin, for example, headaches, hepatitis, cystitis, etc.        TENS, as utilized heretofore, is of no curative value.        TENS, as utilized heretofore, is a symptomatic treatment that suppresses pain sensation that would otherwise serve as a protective mechanism on the outcome of the clinical process.        Safety of TENS devices for use during pregnancy or delivery has not been established.        TENS devices, as utilized heretofore, can affect the operation of demand type cardiac pacemakers.        Do not use TENS on the eyes.        Do not place electrodes directly over the carotid sinus nerves or arteries and laryngeal or pharyngeal muscles.        Do not apply TENS for undiagnosed pain syndromes until etiology (actual cause) is established.        Do not place a TENS electrodes as utilized heretofore in any position that allows current to flow transcerebrally (through the head).        Do not use TENS on broken skin or on areas where normal sensation is absent.        Do not use TENS on children under the age of 12 unless under medical supervision.        
Additionally, there is a growing consensus that the published (prescribed) utilization of electrostimulatory devices such as TENS devices heretofore may be promoting adverse neuromodulatory effects that simply promote the ‘masking’ of pain while concomitantly possibly promoting exacerbating maladaptive neuroplastic changes likely at the expense of true remediation. In fact, the mechanisms employed to perfect the ‘masking’ of pain perception are known to often be responsible for a degree of deleterious ‘maladaptive’ neuroplasticity and metaplastic changes that may ultimately contribute to the ‘chronification’ of pain. [Flor, et al '94]